Long-acting antiretrovirals can address barriers to HIV pre-exposure prophylaxis (PrEP), such as stigma and adherence. In two phase 3 trials, twice-yearly subcutaneous lenacapavir was safe and highly efficacious for PrEP in diverse populations. Furthering long-acting PrEP efforts, this study assessed the pharmacokinetics and safety of two once-yearly intramuscular lenacapavir formulations.

The impact of digital adherence technologies on tuberculosis treatment outcomes remains poorly understood. We investigated whether smart pillboxes and medication labels can reduce poor treatment outcomes in patients with tuberculosis.

Brain infections pose substantial challenges in diagnosis and management and carry high mortality and morbidity, especially in low-income and middle-income countries. We aimed to improve the diagnosis and early management of patients admitted to hospital (adults aged 16 years and older and children aged >28 days) with suspected acute brain infections at 13 hospitals in Brazil, India, and Malawi.

Tuberculosis is a leading cause of death globally. Given the airborne transmission of tuberculosis, anybody can be infected, but people in high-incidence settings are more exposed. Risk of progression to disease is higher in the first years after infection, and in people with undernourishment, immunosuppression, or who smoke, drink alcohol, or have diabetes. Although cough, fever, and weight loss are hallmark symptoms, people with tuberculosis can be asymptomatic, so a high index of suspicion is required. Prompt diagnosis can be made by sputum examination (ideally with rapid molecular tests), but chest radiography can be helpful. Most people with disease can be treated with regimens of 6 months or less; longer regimens may be necessary for those with drug resistance. Central to successful treatment is comprehensive, person-centred care including addressing key determinants, such as undernourishment, smoking, and alcohol use, and optimising management of comorbidities, such as diabetes and HIV. Care should continue after treatment ends, as long-term sequelae are common. Prevention relies mostly on treatment with rifamycin-based regimens; current vaccines have limited efficacy. Ongoing research on shorter and safer regimens for infection and disease treatment, and simpler and more accurate diagnostic methods will be key for tuberculosis elimination.

Ivonescimab is a bispecific antibody against programmed cell death protein 1 and vascular endothelial growth factor, yielding promising clinical outcomes for patients with advanced non-small cell lung cancer in early-phase studies. We compared the efficacy and safety of ivonescimab with pembrolizumab in patients with programmed cell death ligand-1 (PD-L1)-positive advanced non-small cell lung cancer.

Malaria remains a leading cause of illness and death globally, with countries in sub-Saharan Africa bearing a disproportionate burden. Global high-resolution maps of malaria prevalence, incidence, and mortality are crucial for tracking spatially heterogeneous progress against the disease and to inform strategic malaria control efforts. We present the latest such maps, the first since 2019, which cover the years 2000-22. The maps are accompanied by administrative-level summaries and include estimated COVID-19 pandemic-related impacts on malaria burden.

Tocolytics are recommended in international guidelines as treatment for threatened preterm birth. Atosiban, an oxytocin receptor antagonist, is a registered tocolytic drug specifically indicated for the treatment of threatened preterm birth. Although tocolytics have been shown to delay birth, benefits on neonatal outcomes have not been demonstrated. In the APOSTEL 8 trial we aimed to assess superiority of tocolysis with atosiban compared with placebo in threatened preterm birth from 30 weeks and 0 days (30+0 weeks) to 33+6 weeks of gestation in improving neonatal morbidity and mortality.

Overweight and obesity is a global epidemic. Forecasting future trajectories of the epidemic is crucial for providing an evidence base for policy change. In this study, we examine the historical trends of the global, regional, and national prevalence of adult overweight and obesity from 1990 to 2021 and forecast the future trajectories to 2050.

Despite the well documented consequences of obesity during childhood and adolescence and future risks of excess body mass on non-communicable diseases in adulthood, coordinated global action on excess body mass in early life is still insufficient. Inconsistent measurement and reporting are a barrier to specific targets, resource allocation, and interventions. In this Article we report current estimates of overweight and obesity across childhood and adolescence, progress over time, and forecasts to inform specific actions.

Chronic rhinosinusitis with nasal polyps (CRSwNP) symptoms are frequently driven by type 2 inflammation. Depemokimab is the first ultra-long-acting biological drug engineered with enhanced interleukin-5 binding affinity, high potency, and an extended half-life, enabling twice per year dosing and sustained type 2 inflammation inhibition. The ANCHOR-1 and ANCHOR-2 trials investigated the efficacy and safety of depemokimab in people with CRSwNP.

The WHO Global Oral Health Action Plan has set an overarching global target of achieving a 10% reduction in the prevalence of oral conditions by 2030. Robust and up-to-date information on the global burden of oral conditions is paramount to monitor progress towards this target. The aim of this systematic data analysis was to produce global, WHO region, and country-level estimates of the prevalence of, and disability-adjusted life-years (DALYs) attributed to, untreated caries, severe periodontitis, edentulism, other oral disorders, lip and oral cavity cancer, and orofacial clefts from 1990 to 2021.

Haemophilia A and B are congenital X-linked bleeding disorders resulting from deficiencies in clotting factors VIII (haemophilia A) and IX (haemophilia B). Patients with severe deficiency, defined as having less than 1% of normal plasma factor activivity, often have spontaneous bleeding within the first few years of life. Those with moderate and mild deficiencies typically present with post-traumatic or post-surgical bleeding later in life. A high index of suspicion and measurement of factor activity in plasma facilitates early diagnosis. In the 21st century, therapeutic advances and comprehensive care have substantially improved both mortality and morbidity associated with these conditions. Management strategies for haemophilia include on-demand treatment for bleeding episodes and all surgeries and regular treatment (ie, prophylaxis) aimed at reducing bleeds, morbidity, and mortality, thereby enhancing quality of life. Treatment options include factor replacement therapy, non-replacement therapies that increase thrombin generation, and gene therapies that facilitate in vivo clotting factor synthesis. The therapies differ in their use for prophylaxis and on-demand treatment, the mode and frequency of administration, duration of treatment effect, degree of haemostatic protection, and side-effects. Monitoring the effectiveness of these prophylactic therapies involves assessing annual bleeding rates and joint damage. Personalised management strategies, which align treatment with individual goals (eg, playing competitive sports), initiated at diagnosis and maintained throughout the lifespan, are crucial for optimal outcomes. These strategies are facilitated by a multidisciplinary team and supported by clinician-led education for both clinicians and patients.

In patients with venous thromboembolism at high risk of recurrence for whom extended treatment with direct oral anticoagulants has been indicated, the optimal dose is unknown. We aimed to assess efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants in patients in whom extended anticoagulation has been indicated.

Critical illness represents a major global health-care burden and critical care is an essential component of hospital care. There are few data describing the prevalence, treatment, and outcomes of critically ill patients in African hospitals.

Direct oral anticoagulants (DOACs) reduce the rate of thromboembolism in patients with atrial fibrillation but the benefits and risks in survivors of intracerebral haemorrhage are uncertain. We aimed to determine whether DOACs reduce the risk of ischaemic stroke without substantially increasing the risk of recurrent intracerebral haemorrhage.

Data to support individualised choice of optimal glucose-lowering therapy are scarce for people with type 2 diabetes. We aimed to establish whether routinely available clinical features can be used to predict the relative glycaemic effectiveness of five glucose-lowering drug classes.

Schistosomiasis is a neglected tropical disease caused by infection with blood flukes of the genus Schistosoma. Widely distributed in the Middle East, southeast Asia, Latin America, and (mostly) sub-Saharan Africa, schistosomiasis is acquired upon skin penetration of infective larvae released by freshwater snails. Acute infection might present with self-limiting hypersensitivity reactions (known as Katayama fever). Chronic infection typically leads to two main clinical patterns: intestinal or urogenital schistosomiasis, depending on the infecting species. Impairment of other body sites (eg, the CNS or respiratory tract) can occur. The intestinal form is characterised by abdominal pain and diarrhoea, with or without blood; complications are hepatic fibrosis, portal hypertension, splenomegaly, and variceal bleeding. The urogenital form is characterised by dysuria and haematuria; complications are renal failure and squamous-cell carcinoma of the bladder. Conventional diagnosis is based on egg detection in faeces or urine, although sensitivity might be low. Praziquantel is the first-line treatment, and it is also provided in preventive chemotherapy campaigns by mass drug administration to afflicted communities.

Retinal dystrophy caused by genetic deficiency of AIPL1 causes severe and rapidly progressive impairment of sight from birth. We sought to evaluate whether early intervention by gene supplementation therapy was safe and could improve outcomes in children with this condition.

Atopic dermatitis is the most common chronic inflammatory skin disease globally. Key features include an eczematous eruption accompanied by intense itch, which can have an enormous negative effect on patients' quality of life, especially in those with moderate-to-severe disease. Atopic dermatitis is part of a spectrum of atopic conditions that can also include several non-cutaneous organs such as respiratory (eg, allergic rhinitis and asthma) and gastrointestinal (eg, food allergy) systems. For decades, long-term disease control and maintenance were particularly challenging given that treatment options were limited to broad topical and systemic immunosuppressive agents. However, better insights into the pathophysiology of this condition over the past decade have led to the development and approval of safe and efficacious novel targeted treatment approaches. The updated pathophysiological understanding and the evolving therapeutic landscape of atopic dermatitis are discussed in this Seminar.

Nerinetide is a neuroprotectant effective in preclinical models of acute ischaemic stroke when administered within 3 h of onset. However, the clinical evaluation of neuroprotectants in this short timeframe is challenging. We sought to establish the feasibility, safety, and effectiveness of nerinetide when given before hospital arrival within 3 h of symptom onset of suspected stroke.